Serum and tissue levels of atorvastatin and its hydroxylated metabolites (o-hydroxyatorvastatin and p-hydroxyatorvastatin) as measured by tandem mass spectrometry at baseline and at 3 months [ Designated as safety issue: No ]

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer

Official Title ICMJE

A Phase I Prevention Study of Atorvastatin in Women at Increased Risk for Breast Cancer

Brief Summary

Chemoprevention is the use of certain drugs to keep cancer from forming. The use of atorvastatin (Lipitor) may prevent breast cancer. This randomized phase I trial is studying the best dose of atorvastatin in preventing breast cancer in women at increased risk for breast cancer.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the minimum biological effective dose (MBED) of atorvastatin required to induce modulation in the proliferation marker, Ki-67, in breast tissue of women who are at high risk to develop breast cancer. We will evaluate pre- and post atorvastatin treatment (4 dose levels) expression of Ki-67 in samples obtained via FNA from breast tissue of women at high risk for breast cancer. This specific aim tests the hypothesis that treatment with atorvastatin will induce a decrease in Ki-67.

II. To determine plasma and tissue levels of atorvastatin and two of its hydroxylated metabolites (ohydroxyatorvastatin and p-hydroxyatorvastatin) in women who are treated with atorvastatin and to correlate these levels with Ki-67 levels. III. To correlate changes in Ki-67 and the above-described panel of biomarkers with HMG-CoA reductase genotype.

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Enrollment ICMJE

66

Completion Date

October 2012

Primary Completion Date

October 2012 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Women at increased risk for breast cancer, defined by one of the following:

5 year projected Gail risk of greater than 1.67%

Previous diagnosis of atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) (per participating institution's pathology review), or ductal carcinoma in situ (participants could have received any type of surgery and radiation as long as they have an intact opposite breast)

The participant must have been properly informed of the study and must sign an informed consent to be able to be enrolled in the study; the informed consent document must be signed, witnessed, and dated prior to start of the study

Normal physical exam and bilateral mammogram that shows no evidence of suspicious, malignant disease, or uncharacterized lesions within last 12 months and no evidence of any active other cancer

The effects of atorvastatin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential must agree to use adequate contraception (barrier method of birth control (IUD); abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately

Chronic medical condition that requires regular use of statins or steroids (unless participants have discontinued these drugs 1 month prior to enrollment)

Participants may not be receiving any other investigational agents

History of allergic reactions attributed to compounds of similar chemical or biologic composition to atorvastatin

Psychiatric condition, including history of clinical depression, or addictive disorder that would preclude obtaining informed consent or would interfere with compliance; uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant women are excluded from this study because atorvastatin is a Class X agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atorvastatin breast feeding should be discontinued if the mother is treated with atorvastatin

Gender

Female

Ages

18 Years to 72 Years (Adult, Senior)

Accepts Healthy Volunteers

Yes

Contacts ICMJE

Contact information is only displayed when the study is recruiting subjects